Dimethylamine → benzyl 4-[(1R,2S)-2-(2-{4-[2-(dimethylamino)-2-oxoethyl]-2,5-difluorophenoxy}ethyl)cyclopropyl]piperidine-1-carboxylate

Participants

Reaction Steps

To a solution of {4-[2-((1S,2R)-2-{1-[(benzyloxy)carbonyl]piperidin-4-yl}cyclopropyl)ethoxy]-2,5-difluorophenyl}acetic acid (313 mg, 0.661 mmol) in 2.5 ml anhydrous DMF at RT was added dimethylamine (2.0 M solution in THF, 0.661 ml, 1.32 mmol) and N, N-diisopropylethylamine (0.562 ml, 3.31 mmol). 0-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (503 mg, 1.32 mmol) was then added to the solution and the mixture stirred at RT overnight. The reaction was quenched by addition of water (12 ml) and the mixture extracted with ethyl acetate (12 ml). The layers were separated and the organic layer was dried over sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (Biotage column, 25 g) using a gradient eluent of 0-50% ethyl acetate in hexanes (800 ml) to afford the title compound. LC/MS (m/z): 501.4 (M+H)+.

Provenance & Evidence